Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21201, USA.
Stem Cells. 2012 Nov;30(11):2548-60. doi: 10.1002/stem.1214.
Radiation therapy is a part of the standard treatment for brain tumor patients, often resulting in irreversible neuropsychological deficits. These deficits may be due to permanent damage to the neural stem cell (NSC) niche, damage to local neural progenitors, or neurotoxicity. Using a computed tomography-guided localized radiation technique, we studied the effects of radiation on NSC proliferation and neuroblast migration in the mouse brain. Localized irradiation of the subventricular zone (SVZ) eliminated the proliferating neural precursor cells and migrating neuroblasts. After irradiation, type B cells in the SVZ lacked the ability to generate migrating neuroblasts. Neuroblasts from the unirradiated posterior SVZ did not follow their normal migratory path through the irradiated anterior SVZ. Our results indicate that the migrating neuroblasts were not replenished, despite the presence of type B cells in the SVZ post-irradiation. This study provides novel insights into the effects of localized SVZ radiation on neurogenesis and cell migration that may potentially lead to the development of new radiotherapy strategies to minimize damage to NSCs and neuroblast migration.
放射治疗是脑肿瘤患者标准治疗的一部分,常导致不可逆转的神经心理学缺陷。这些缺陷可能是由于神经干细胞(NSC)龛位的永久性损伤、局部神经祖细胞的损伤或神经毒性所致。我们使用计算机断层扫描引导的局部放射技术,研究了放射对小鼠脑内 NSC 增殖和神经母细胞迁移的影响。对侧脑室下区(SVZ)的局部照射消除了增殖的神经前体细胞和迁移的神经母细胞。照射后,SVZ 中的 B 型细胞丧失了产生迁移神经母细胞的能力。来自未照射的后 SVZ 的神经母细胞没有遵循它们正常的通过照射的前 SVZ 的迁移路径。我们的结果表明,尽管 SVZ 中有 B 型细胞存在,但迁移的神经母细胞并没有得到补充。这项研究提供了关于局部 SVZ 放射对神经发生和细胞迁移的影响的新见解,这可能会导致开发新的放疗策略,以最大限度地减少对 NSCs 和神经母细胞迁移的损伤。